International Symposium I (Management of antibiotics-resistant Helicobacter pylori infection) Perspectives from Viet Nam Vu Van Khien 1,HoDangQuyDung 2, Tran Thanh Binh 2 1 Department of GI Endoscopy, 108 Central Hospital; 2 Choray Hospital, Vietnam [CURRICULUM VITAE] Current position - Head, Dept. of Diagnostic Endoscopy, 108 Military Central Hospital. - General Secretary, Vietnam Association of Gastroenterolgy (VNAGE) - Vice President, Vietnam Federation Association of Digestive Endoscopy 1983-1989 MD, Military Medical University, Hanoi-Vietnam 1995-2000 Ph.D, Military Medical University, Hanoi-Vietnam 1990-1991 Resident, Department of Internal Medicine-Gastroenterology (Clinical), 108 Military Central Hospital -Hanoi -Vietnam 1990-1991 Fellowship, Department of Internal Medicine-Gastroenterology (Clinical), 108 Military Central Hospital and Hanoi Medical University-Hanoi -Vietnam 2000 Ass. Professor, Ministry of Education and Training- Hanoi-Vieetnam [ABSTRACT] Introduction Helicobacter pylori (H. pylori) has high prevalence in Southeast Asian contries and has been linked to the development of gastric inflammation, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. 1,2 H. pylori infection is very common in Vietnam, the situation being similar to that in many other developing countries. Most large-scale studies have repoted that prevalence of H. pylori infection is over 70% among adults and significantly lower in children. 3,20,21 A hospital survey reported a H. pylory prevalence rate of 59.9-69.9% in chronic gastritis, 77.8% in gastric ulcer, 85-95% in duodenal ulcer 37
and 85.3-93.6% in combined gastric and duodenal ulcer. 22,23 Generally, H. pylori eradication is indicated in cases of PU including active, non-active and complicated, gastric MALT lymphoma, and to some extent, chronic gastritis and functional dyspepsia. Eradication of H. pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer. 4-8 We synthesized studies in Vietnam on the antibiotic resistance of H. pylori. Methods - Evaluation of H. pylori infection rate in gastroduodenal diseases in Vietnam - Evaluation of H. pylori resistance rate in Vietnam - The causes of drug resistance of H. pylori Results In Vietnam, in the last decade (1990-2000), triple therapy regimens including 1 proton pump inhibitor (PPI) or histamin H2 and two antibiotics such as amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVFX), and tetracycline (TC) have been widely used to eradicate this bacterium. But, there have been no official recommendations regarding first line, second line and rescue therapies. Therefore, CLR- and/or MNZ-based triple therapy is commonly used as the standard primary regimen for the treatment of H. pylori infection on the basis of the international consensus reports. 7,12,13 Moreover, in many cases, eradication treatment may be initiated without adequate evidence of infection, as diagnostic test for H. pylori are not widely available. Patients compliance and adherence to treatment are often unsatisfactory. After alleviation by prescribed drugs, many patients do not return to hospital for confirmation of eradication because of concern about medical expenses, making follw-up extremely difficult. Additionally, the widespread practice of self-medication is another problematic issue that undoutedly contributes to the increasing incidence of antibiotic resistance in Vietnam. Although the success of the treatment depends on several factors such as smoking and patient compliance, antibiotic resistance is the most common factor causing failure of treatment. 9-11 A placebo controlled clinical study has reported that a regimen comprising lansoprazole, clarithromycin and tinidazole twice daily achieved an eradication rate of 96% in Vietnamese patients infected with metronidazole sensitive H. pylori, but only 79% and as low as 57% among those infected with low-level resistant and high-level resistant strains, respectively. Unfortunately, antibiotic resistance is common among Vietnamese H. pylori 38
Van Khien Vu: Perspectives from Viet Nam strains. Our unpublished data show that while resistance to amoxicillin and tetracycline is rare, strains resistant to metronidazole, clarithromycin and levofloxacin are prevalent, with incidence about 73%, 31% and 19%, respectively; while the rate of multidrug resistance is estimated at over 8%. In addition, over one-third of resistance strains can be regarded as high-level resistant. For the above reasons, the eradication rate in Vietnam is not as high as that in developed countries. The cure rate achieved by triple therapies has varied to a great extent among studies. H. pylori eradication ability has been reduced from 91.7% (2003) to 62.5% (2012). 14,15 Among the 220 H. pylori strains for susceptibility test were isolated from Hanoi, Hue and Hochiminh for determining the minimum inhibitory concentrations of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MET), levofoxacin (LVFX), tetracillin (TC). 23 The resistance rates were 7.7% (AMX), 43.6% (CLR), 83.6% (MNZ), 32.2% (LVFX) and 10.9% (TC). Resistance to both CLR and MNZ was most commonly observed (36.8%). 58.2% of H. pylori strains were resistant at least to 2 antibiotics or more. In contract, bismuth-based quadruple regimens are likely to yield the highest eradication rate and thus can be used as a rescure therapy if the first-line treatment has failed. 23 Recently, several groups worldwide have included levofloxacin in the eradication regimen and encouraging results. 18-19 As levofloxacin is rarely used to treat H. pylori infection in Vietnam, one group have investigated the efficacy of levofloxacin-containing triple regimen as a second-line therapy for Vietnam patients. However, the results were very disappointing, with an eradication rate as low as 59%, 17 which was perhaps partly attributable to the rather high prevalence of levofloxacin resistance. Conclusions High incidence of resistance to CLR, LVFX and MNZ suggests that standard triple therapies may not be useful as first-line treatment. Alternative strategies such as bismuth-based quadruple therapies may be more effective. References 1. Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2(1):28-37. 2. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347(15):1175-1186. 3. Hoang TT, Bengtsson C, Phung DC et al. Seroprevalence of Helicobacter pylori infection in urban and rural Vietnam. Clin Diagn Lab Immunol 2005;12:81-85 39
4. Shiota S, Yamaoka Y. Management of Helicobacter pylori. F1000 Med Rep. 2010:2. 5. Hosking SW, Chung SCS, Yung MY et al. Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial. The Lancet. 1994;343(8896):508-510. 6. Shiota S, Murakami K, Fujioka T et al. Population-based strategies for Helicobacter pylori associated disease management: a Japanese perspective. Expert Rev Gastroenterol Hepatol. 2010;4(2):149-156. 7. Malfertheiner P, Megraud F, O Morain C et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56(6):772-781. 8. Takenaka R, Okada H, Kato J et al. Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type. Alimentary Pharmacology & Therapeutics. 2007;25(7):805-812. 9. Qasim A, O Morain CA. Review article: treatment of Helicobacter pylori infection and factors influencing eradication. Aliment Pharmacol Ther. 2002;16(Suppl 1):24-30. 10. Jenks PJ. Causes of failure of eradication of Helicobacter pylori. BMJ. 2002;325(7354):3-4. 11. Suzuki T, Matsuo K, Ito H et al. Smoking increases the treatment failure for Helicobacter pylori eradication. Am J Med. 2006;119(3):217-224. 12. Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-1825. 13. Fock KM, Katelaris P, Sugano K et al. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 2009;24(10):1587-1600. 14. Vinh NT, Hop TV, Loi HG et al. The effectiveness of twice-daily first line therapy (OAC, OAM, OMC) and the second line therapy (OAC, OMBT) for the patients with Helicobacter pylori positive gastroduodenal ulcer. 4th Congress on Gastroenterology of Southeast Asian Nations 2004, Oct 15-18th, Hanoi. (Vietnamese with Enghlish summary). 15. Minh DC, Hoang BH. Assessment of antibiotic resistance of Helicobacter pylori in patients with duodenal ulcer treated with eradicating failure. Vietnamese Journal of Gastroenterology 2010;8:645-650 (in Vietnamese with Enghlish summary). 16. Mao HV, Lac BV, Long T et al. Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: A randomized, controlled trial in Vietnamese patients with duodenal. Aliment Pharmacol Thera 2000;14:97-101 17. Trung TT, Duc QT, Huong LK. The effectiveness of EAL and EBMT regimens as the second line therapies in Helicobacter pylori eradication. Vietnamese Journal of Gastroenterology 2008;3:730-735 (in Vietnamese with Enghlish summary). 18. Saad RJ, Schoenfield P, Kim HM et al. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. 40
Van Khien Vu: Perspectives from Viet Nam Am J Gastroenterol 2006;101:488-496 19. Gisbert JP, Fernandez-Bermejo M, Molina-InfanteJetal.First-linetripletherapywithlevofloxacin for Helicobacter pylori eradication. Aliment Pharmacol Thera 2007;26:495-500. 20. Nguyen BV, Nguyen KG, Phung CD et al. Prevalence of and factors associated with Helicobacter pylori infection in children in the north of Vietnam. Am J Trop Med Hyg 2006;74:536-539 21. Nguyen BV, Nguyen GK, Phung CD et al. Intra-familial transmission of Helicobacter pylori infection in children of households with multiple generations in Vietnam. Eur J Epidemiol 2006;21:459-463 22. Nguyen LT, Uchida T, Tsukamoto, Trinh TD, Long T et al. Evaluation of Rapid Urine Test for the detection of Helicobacter pylori Infection in the Vietnamese Population. Digestive diseases and Science 2010;55:89-93 23. Dung HD, Binh TT, Khien VV et al. The incidence of antibiotic resistance of Helicobacter pylori. Vietnamese Journal of Gastroenterology 2015;6:830-836 (in Vietnamese with Enghlish summary). 41